Taxanes, such as paclitaxel, docetaxol and cabazitaxel, exert their cytotoxic effects via interaction with tubulin subunits, the building blocks of microtubules. Microtubules, formed by polymerization of heterodimeric α- and β-tubulin subunits, play fundamental roles in a wide range of cellular processes, such as maintenance of cell shape, cell signaling and cell division (Gelfand and Bershadsky, 1991). By stabilizing microtubules and inhibiting disassembly to tubulin monomers, taxanes interfere with proper formation of the mitotic spindle, resulting in activation of the mitotic spindle check point and mitotic arrest (Schiff et al., 1979). Drug-treated cells eventually escape mitotic arrest without assembling a normal mitotic spindle. Depending on the cell type and concentration of taxanes used, these cells will either undergo apoptosis during mitotic arrest or as a result of the abnormal mitosis (Shi et al., 2008). The mechanisms of taxane-induced apoptosis are poorly understood, but involve both phosphorylation of Bcl-2 and activation of caspases-3 and -9 (Haldar et al., 1996; Perkins et al., 1998).
Since the U.S. Food and Drug Administration (FDA) originally approved paclitaxel for clinical use for advanced ovarian cancer in 1992, it has shown significant activity against a broad spectrum of solid malignancies. At present, taxanes, either as single-agents or in combination with multiple other cytotoxic agents, are routinely used in the adjuvant, neoadjuvant and metastatic setting for a wide range of solid malignancies, including those of the breast, prostate, ovary, lung, and head and neck (Chu et al., 2005; Dombernowsky et al., 1996; Mackler and Pienta, 2005; Wakelee et al., 2005). Despite its widespread use, the clinical effectiveness of taxanes is limited by the emergence of taxane-resistant cancer cells, which ultimately leads to relapse and worsens prognosis.